Search

Background: Traditional psychometric measures aimed at characterizing the pain experience often show considerable overlap, due to interlinked affective and modulatory processes under central nervous system control. Neuroimaging studies have been employed to investigate this complexity of pain processing, in an attempt to provide a quantifiable, adjunctive description of pain perception. In this exploratory study, we examine psychometric and neuroimaging data from 38 patients with painful osteoarthritis of the carpometacarpal joint. We had two aims: first, to utilize principal component analysis (PCA) as a dimension reduction strategy across multiple self-reported endpoints of pain, cognitive and affective functioning; second, to investigate the relationship between identified dimensions and regional cerebral blood flow (rCBF) as an indirect measure of brain activity underpinning their ongoing pain experiences.Methods: Psychometric data were collected using validated questionnaires. Quantitative estimates of rCBF were acquired using pseudo-continuous arterial spin-labelled functional magnetic resonance imaging.Results: Two principal components were identified that accounted for 73% of data variance; one related to pain scores and a second to psychological traits. Voxel-wise multiple regression analysis revealed a significant negative association between the 'pain score' component and rCBF to a right temporal lobe cluster, including the amygdala and the parahippocampal cortex.Conclusion: We suggest this association may represent a coping mechanism that aims to reduce fear-related pain-anxiety. Further investigation of central brain processing mechanisms in osteoarthritis-related pain may offer insights into more effective therapeutic strategies.Significance: This study demonstrates that dimension reduction using PCA allows insight into pain perception and its affective components in relation to brain activation patterns in patients with painful hand osteoarthritis. [ABSTRACT FROM AUTHOR]

Objective Cryopyrin-associated periodic syndromes ( CAPS) result from gain-of-function mutations in the NLRP3 gene, which causes excessive release of interleukin-1β ( IL-1β) and systemic inflammation. While pathogenetic NLRP3 variant phenotypes are well-characterized, low-penetrance NLRP3 variants represent a significant clinical challenge. The aims of this study were to determine the clinical phenotype, the in vitro biologic phenotype, and the effect of anti- IL-1 treatment in patients with low-penetrance NLRP3 variants. Methods A multicenter study of consecutive symptomatic patients with low-penetrance NLRP3 variants recruited from 7 centers between May 2012 and May 2013 was performed. The observed findings were transferred into a study database, from which they were extracted for analysis. Controls were patients with a known pathogenetic NLRP3 variant. Clinical presentation and CAPS markers of inflammation were captured. Functional assays of inflammasome activation, including caspase 1 activity, NF-κB release, cell death, and IL-1β release, were performed. Treatment effects of IL-1 were determined. Comparisons between low-penetrance and pathogenetic NLRP3 variants were performed. Results The study included 45 patients, 21 of which were female (47%); 26 of the patients (58%) were children. NLRP3 low-penetrance variants identified in the patients were Q703K (n = 19), R488K (n = 6), and V198M (n = 20). In the controls, 28 had pathogenetic NLRP3 variants. Patients with low-penetrance NLRP3 variants had significantly more fever (76%) and gastrointestinal symptoms (73%); eye disease, hearing loss, and renal involvement were less common. Functional inflammasome testing identified an intermediate phenotype in low-penetrance NLRP3 variants as compared to wild-type and pathogenetic NLRP3 variants. All treated patients responded to IL-1 inhibition, with complete response documented in 50% of patients. Conclusion Patients with low-penetrance NLRP3 variants display a distinct clinical phenotype and an intermediate biologic phenotype, including IL-1β and non- IL-1β-mediated inflammatory pathway activation. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 71-year old woman with systemic mastocytosis with history of smoking. It is noted that she was further diagnosed with tripe palms that are characterized clinically by thickened velvety palms with pronounced dermatoglyphics. The article mentions that Anaplastic lymphoma kinase (ALK) fusion oncogenes represent a novel molecular target in a small subset of non-small cell lung cancers (NSCLC).

Background Recurrent angioedema ( Rec A) is a frequent clinical problem characterized by suddenly occurring cutaneous and/or mucosal swellings. Depending on their location, Rec A may be painful, hindering, disfiguring, or even life-threatening. The assessment of disease activity in affected patients is important to guide treatment decisions. Currently, however, there is no standardized and validated outcome measure available to do so. Objective To develop and validate the first specific patient-reported outcome instrument to assess disease activity in Rec A patients, the Angioedema Activity Score ( AAS). Methods After a set of potential AAS items was developed, item evaluation and reduction were performed by means of impact analysis, factor analysis, regression analysis, and by checking for face validity. In addition, the items of the final AAS questionnaire were tested for their validity and reliability during a 12-week validation study. Results In total, data from 110 and 80 Rec A patients were used during the AAS item evaluation and validation phase, respectively. The resulting AAS consisted of five items and was found to have a one-dimensional structure and excellent internal consistency. It correlated well with other measures of disease activity and quality-of-life impairment, thus demonstrating its convergent validity. In addition, the known-groups validity and test-retest reliability of the AAS were found to be good. Conclusions The AAS is the first validated and reliable tool to determine disease activity in Rec A patients, and it may serve as a valuable instrument in future clinical studies and routine patient care. [ABSTRACT FROM AUTHOR]

Reduction of flux through photorespiration has been viewed as a major way to improve crop carbon fixation and yield since the energy-consuming reactions associated with this pathway were discovered. This view has been supported by the biomasses increases observed in model species that expressed artificial bypass reactions to photorespiration. Here, we present an overview about the major current attempts to reduce photorespiratory losses in crop species and provide suggestions for future research priorities. [ABSTRACT FROM AUTHOR]

Background Cold contact urticaria ( CCU) is characterized by itchy wheal and flare responses due to the release of histamine and other pro-inflammatory mediators after exposure to cold. The treatment of choice is nonsedating antihistamines, dosages of which may be increased up to fourfold if standard doses are ineffective. Here, we assess the effects of a standard 20 mg dose and up-dosing to 40 and 80 mg of bilastine in reducing the symptoms of CCU and inflammatory mediator release following cold challenge. Methods Twenty patients with CCU were included in this randomized, crossover, double-blind, placebo-controlled 12-week study. They received placebo, 20, 40 or 80 mg of bilastine daily each for 7 days with 14-day washout periods. The primary readout was change in critical temperature thresholds ( CTT). Secondary readouts were changes in pruritus, levels of histamine IL-6, IL-8 and TNF-α collected by skin microdialysis and safety and tolerability of bilastine. Results Bilastine 20 mg was highly effective ( P < 0.0001) in reducing CTT. Up-dosing to 80 mg significantly ( P < 0.04) increased its effectiveness. At this dose, 19 of 20 (95%) patients responded to treatment, with 12 of 20 (60%) becoming symptom free. Only one patient was refractory to treatment. Microdialysis levels of histamine, IL-6 and IL-8 assessed 1-3 h after cold challenge were significantly ( P < 0.05) decreased following up-dosing with 80 mg bilastine. Bilastine treat-ment was well tolerated without evidence of increased sedation with dose escala-tion. Conclusions Bilastine was effective in reducing the symptoms of patients with CCU. Increased efficacy of bilastine with fourfold up-dosing was without sedation and supports urticaria treatment guidelines. [ABSTRACT FROM AUTHOR]

Background Mastocytosis is frequently associated with mast cell-mediated symptoms which require relieving medication. While second generation antihistamines (sg AHs) are the first line therapeutic strategy to treat mast cell mediator-related symptoms, controlled clinical trials on how they improve quality of life have not been performed. Methods This randomized, double-blind, placebo-controlled, cross-over trial assessed rupatadine 20 mg daily in the treatment of mastocytosis symptoms in 30 adult patients. Symptoms were assessed by a visual analogue scale ( VAS) and symptom specific quality of life questionnaire ( Itchy Qo L). Results The mean Itchy Qo L total score and VAS symptom score were significantly improved in the rupatadine treatment phase compared with placebo. There were also significant reductions from placebo in the severity of itch, wheal and flare, flushing, tachycardia and headache but not gastrointestinal symptoms. Conclusions In this first comprehensive trial of a sg AH in mastocytosis, rupatadine 20 mg daily for 4 weeks significantly controlled symptoms and improved patients' quality of life. [ABSTRACT FROM AUTHOR]

Background Chronic urticaria is a common disorder characterized by recurrent wheals, angioedema, or both. Several differential diagnoses need to be considered in patients presenting with wheals and/or angioedema. These include rare diseases such as autoinflammatory syndromes and urticarial vasculitis in patients with recurrent wheals and bradykinin-mediated angioedema in patients with recurrent swellings. Aim and Result In order to not miss these conditions, we have developed a symptom-based diagnostic algorithm for the management of patients with wheals and/or angioedema. Discussion and Conclusion By asking the right questions and performing a limited diagnostic workup as suggested here, this algorithm may help to establish the right diagnosis and treat patients early and more effectively. [ABSTRACT FROM AUTHOR]

Schnitzler's syndrome is characterized by recurrent urticarial rash and monoclonal gammopathy, associated with clinical and biological signs of inflammation and a long-term risk of AA amyloidosis and overt lymphoproliferation. An extensive literature review was performed, and the following questions were addressed during an expert meeting: In whom should Schnitzler's syndrome be suspected? How should the diagnosis of Schnitzler's syndrome be established? How should a patient with Schnitzler's syndrome be treated? How should a patient with Schnitzler's syndrome be followed up?. A diagnosis of Schnitzler's syndrome is considered definite in any patient with two obligate criteria: a recurrent urticarial rash and a monoclonal IgM gammopathy, and two of the following minor criteria: recurrent fever, objective signs of abnormal bone remodeling, elevated CRP level or leukocytosis, and a neutrophilic infiltrate on skin biopsy. It is considered probable, if only 1 minor criterion is present. In patients with monoclonal IgG gammopathies, diagnosis is definite if three minor criteria are present and possible if two are present. First-line treatment in patients with significant alteration of quality of life or persistent elevation of markers of inflammation should be anakinra. Follow-up should include clinical evaluation, CBC and CRP every 3 months and MGUS as usually recommended. [ABSTRACT FROM AUTHOR]

Recurrent fever can be the sole or leading manifestation of a variety of diseases including malignancies, autoimmune diseases and infections. Because the differential diagnoses are manifold, no formal guidelines for the approach of patients with recurrent fever exists. The newly recognized group of autoinflammatory diseases are often accompanied by repetitive fever attacks. As these episodes are frequently associated by a variety of divergent presentations, the differentiation of other causes for febrile illnesses can be difficult. In this article, we first review disease entities, which frequently present with the symptom of recurrent fever. In a next step, we summarize their characteristic pattern of disease presentation. Finally, we analyse key features of autoinflammatory diseases, which are helpful to distinguish this group of diseases from the other causes of recurrent fever. Recognizing these symptom patterns can provide the crucial clues and, thus, lead to the initiation of targeted specific diagnostic tests and therapies. [ABSTRACT FROM AUTHOR]

Background Recently, the updated EAACI/GA2LEN/EDF/WAO guidelines for urticaria have been published. Objective To examine how chronic spontaneous urticaria (csU) patients in Germany are diagnosed and treated, and to compare the outcome to the guideline recommendations. Methods During this cross-sectional survey study, most dermatologists, paediatricians and 5149 general practitioners in private practice in Germany were asked to participate. All physicians who agreed were requested to complete a standardized questionnaire about their diagnostic and therapeutic management of csU. Results A total of 776 questionnaires were available for analysis. Most physicians (82%) were attempting to identify underlying causes in their csU patients, but with only limited success. More than 70% reported to check for total serum IgE and to do skin prick testing (not suggested in first line by guideline). In contrast, only 10% applied the autologous serum skin test. The most common first-line treatments were non-sedating antihistamines in standard or higher doses (as recommended). However, many physicians reported still using first generation sedating antihistamines (23%) (not recommended) or systemic steroids (18%). Experience with alternative options was low. Less than one-third of the participants reported to be familiar with the guidelines. Those who did, were found to be more likely to check for underlying causes, to be more experienced with antihistamine updosing and to be more reluctant to use sedating antihistamines or systemic steroids. Conclusion The diagnostic and therapeutic management of csU by private practice physicians does not sufficiently comply with the guidelines. Awareness of the guidelines can lead to improved care. [ABSTRACT FROM AUTHOR]

Background Urticaria is a frequent reason for consultations. Recently, it has been demonstrated that the management of chronic spontaneous urticaria (csU) in the practice setting does not fully comply with published guidelines. In addition, it was shown that one of four csU patients is referred to specialized centres. Objective To analyse the management of urticaria patients in tertiary referral centres. Methods During a standardized expert-to-expert interview, 41 specialists from German tertiary care centres were asked for different aspects of urticaria patient care with a special focus on csU. Results On average, the participating centres saw 25 csU patients per month. All ran programmes for the identification of underlying causes with an average success rate of 45 ± 3% which is considerably higher as has been found in the practice setting. In those patients where an identification succeeds, infections, drugs, intolerance and autoreactivity were reported to be causes in 41%, 20%, 17% and 16%. In their symptomatic treatment the majority of centres (71%) followed the guidelines by using regular dosed non-sedating H1-antihistamines as first line and higher doses (61%) as second line option. In contrast to the practice setting, meaningful experience also existed for alternative therapies in antihistamine-resistant patients, such as dapsone, cyclosporin and omalizumab. The expenditure of time, laboratory costs and frequency of follow-up visits was reported to be above average in case of csU. Conclusion This study indicates that some urticaria patients, especially those with unknown causes or with an H1-antihistamine-resistant disease, may benefit from a referral to tertiary care centres. [ABSTRACT FROM AUTHOR]

Urticarial skin reactions are one of the most frequent problems seen by allergists and clinical immunologists in daily practice. The most common reason for recurrent wheals is spontaneous urticaria. There are, however, several less common diseases that present with urticarial rash, such as urticarial vasculitis and autoinflammatory disorders. The latter include cryopyrin-associated periodic syndrome and Schnitzler's syndrome, both rare and disabling conditions mediated by increased interleukin-1 secretion. Apart from the urticarial rash, patients are suffering from a variety of systemic symptoms including recurrent fever attacks, arthralgia or arthritis and fatigue. Autoinflammatory diseases are often associated with a diagnostic delay of many years and do not respond to antihistamines and other treatments of urticaria. Also, the chronic inflammation may lead to long-term complications such as amyloidosis. It is therefore important not to miss these diseases when diagnosing and treating patients with chronic recurrent urticarial rash. Here, we present clinical clues and tips that can help to identify autoinflammatory disorders in patients presenting with chronic urticarial rash and discuss their clinical picture and management. [ABSTRACT FROM AUTHOR]

Background Recurrent angioedema is a frequent clinical problem characterized by unpredictably and rapidly occurring cutaneous and mucosal swellings. These swellings may be painful and/or disfiguring. Upper airway involvement can also lead to dyspnea and suffocation. Although the disease burden is high, there is currently no specific instrument to measure health-related quality of life (QoL) impairment. Objective To develop and validate the first symptom-specific tool to assess QoL impairment in recurrent angioedema patients, adhering to established methodological recommendations. Methods During the development phase, 29 questions (items) were generated. Subsequently, item reduction was performed by means of impact analysis and factor analysis as well as by checking for content and face validity. As a result, 17 items were selected and included in the final instrument, the Angioedema QoL Questionnaire ( AE-QoL). AE-QoL was then tested for its validity, reliability, and influence factors. Results One hundred and ten angioedema patients took part in the validation of AE-QoL. AE-QoL was found to have a four-dimensional structure as well as a valid total score. All of its four domains (functioning, fatigue/mood, fears/shame, food) showed good levels of internal consistency with Cronbach's alpha > 0.8. Test-retesting revealed a good reliability of the instruments total score and domain scores. Gender as well as the patients' self-rated disease activity was found to be predictors of the AE-QoL total score. Conclusions Angioedema Quality of Life Questionnaire is the first angioedema-specific QoL questionnaire. It is a short, valid and reliable instrument that may serve as a valuable tool in future clinical studies and in routine patient care. [ABSTRACT FROM AUTHOR]

Background Schnitzler syndrome (SchS) is a rare disease with suspected autoinflammatory background that shares several clinical symptoms, including urticarial rash, fever episodes, arthralgia, and bone and muscle pain with cryopyrin-associated periodic syndromes ( CAPS). Cryopyrin-associated periodic syndromes respond to treatment with interleukin-1 antagonists, and single case reports of Schnitzler syndrome have shown improvement following treatment with the interleukin-1 blocker anakinra. This study evaluated the effects of the interleukin-1 antagonist rilonacept on the clinical signs and symptoms of SchS. Methods Eight patients with SchS were included in this prospective, single-center, open-label study. After a 3-week baseline, patients received a subcutaneous loading dose of rilonacept 320 mg followed by weekly subcutaneous doses of 160 mg for up to 1 year. Efficacy was determined by patient-based daily health assessment forms, physician's global assessment (PGA), and measurement of inflammatory markers including C-reactive protein ( CRP), serum amyloid A ( SAA), and S100 calcium-binding protein A12 (S100A12). Results Treatment with rilonacept resulted in a rapid clinical response as demonstrated by significant reductions in daily health assessment scores and PGA scores compared with baseline levels ( P < 0.05). These effects, which were accompanied by reductions in CRP and SAA, continued over the treatment duration. Rilonacept treatment was well tolerated. There were no treatment-related severe adverse events and no clinically significant changes in laboratory safety parameters. Conclusion Rilonacept was effective and well tolerated in patients with SchS and may represent a promising potential therapeutic option ( NCT01045772 [ Identifier]; Eudra CT #2006-004290-97). [ABSTRACT FROM AUTHOR]

Background and Purpose: The chemokine receptor CCR5 is well known for its function in immune cells; however, it is also expressed in the brain, where its specific role remains to be elucidated. Because genetic factors may influence the risk of developing cerebral ischaemia or affect its clinical outcome, we have analysed the role of CCR5 in experimental stroke.Experimental Approach: Permanent cerebral ischaemia was performed by occlusion of the middle cerebral artery in wild-type and CCR5-deficient mice. Locomotor behaviour, infarct size and histochemical alterations were analysed at different time points after occlusion.Key Results: The cerebral vasculature was comparable in wild-type and CCR5-deficient mice. However, the size of the infarct and the motor deficits after occlusion were markedly increased in CCR5-deficient mice as compared with wild type. No differences between wild-type and CCR5-deficient mice were elicited by occlusion with respect to the morphology and abundance of astrocytes and microglia. Seven days after occlusion the majority of CCR5-deficient mice displayed neutrophil invasion in the infarct region, which was not observed in wild type. As compared with wild type, the infarct regions of CCR5-deficient mice were characterized by increased neuronal death.Conclusions and Implications: Lack of CCR5 increased the severity of brain injury following occlusion of the middle cerebral artery. This is of particular interest with respect to the relatively frequent occurrence of CCR5 deficiency in the human population (1-2% of the Caucasian population) and the advent of CCR5 inhibitors as novel drugs. [ABSTRACT FROM AUTHOR]

The study of neuronal differentiation of embryonic stem cells has raised major interest over recent years. It allows a better understanding of fundamental aspects of neurogenesis and, at the same time, the generation of neurons as tools for various applications ranging from drug testing to cell therapy and regenerative medicine. Since the first report of human embryonic stem (ES) cells derivation, many studies have shown the possibility of directing their differentiation towards neurons. However, there are still many challenges ahead, including gaining a better understanding of the mechanisms involved and developing techniques to allow the generation of homogeneous neuronal and glial subtypes. We review the current state of knowledge of embryonic neurogenesis which has been acquired from animal models and discuss its translation into in vitro strategies of neuronal differentiation of ES cells. We also highlight several aspects of current protocols which need to be optimized to generate high-quality embryonic stem cell-derived neuronal precursors suitable for clinical applications. Finally, we discuss the potential of embryonic stem cell-derived neurons for cell replacement therapy in several central nervous system diseases. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Chronic granulomatous disease (CGD), a genetic disorder characterized by the absence of a functional phagocyte NADPH oxidase, is a severe immune deficiency. However, non-infectious hyperinflammation is a second hallmark of the disease. In CGD mouse models, sterile hyperinflammation can be induced by A. fumigatus cell wall preparations. In this study, we used subcutaneous injection of microbial cell walls and cell wall components to identify causes of CGD hyperinflammation and to characterize its histological features. Sterile cell wall preparations from fungi ( A. fumigatus, C. albicans, S. cerevisiae), but not from bacteria ( S. aureus, P. aeruginosa, E. coli), caused prolonged and severe skin inflammation in CGD mice. To identify fungal cell wall elements responsible for this process, we investigated microbial cell wall-derived monosubstances. Injection of β(1-3)(1-6)-glucan induced severe hyperinflammation in CGD mice, while other fungal cell components [mannan, (1-3) β-glucan] or bacterial cell wall components (lipopolysaccharide, lipoteichoic acid) caused no or only moderate inflammation. β-glucan-induced hyperinflammation was predominantly due to a defect in termination of inflammation, as in the initial stage (2 days), the severity of inflammation and the extent of cell death were comparable in wild-type and CGD mice. At later stages (7 days), β(1-3)(1-6)-glucan-induced inflammation had subsided in wild-type mice. In contrast, CGD mice showed persistent severe inflammation with central necrosis, containing abundant apoptotic and necrotic cells. In summary, branched fungal β-glucan induces a severe inflammatory reaction in the absence of phagocyte NADPH oxidase. As opposed to the commonly perceived notion that reactive oxygen species are the cause of cell death, our results demonstrate that tissue necrosis can be caused by the absence of a superoxide-producing enzyme. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Age-associated dementia, in particular Alzheimer's disease (AD), will be a major concern of the 21st century. Research into normal brain aging and AD will therefore become increasingly important. As for other areas of medicine, the availability of good animal models will be a limiting factor for progress. Given the complexity of the human brain, the identification of appropriate primate models will be essential to further knowledge of the disease. In this review, we describe the features of brain aging and age-associated neurodegeneration in a small lemurian primate, the Microcebus murinus, also referred to as the mouse lemur. The mouse lemur has a relatively short life expectancy, and animals over 5 years of age are considered to be elderly. Among elderly mouse lemurs, the majority show normal brain aging, whereas approximately 20% develop neurodegeneration. This Microcebus age-associated neurodegeneration is characterized by a massive brain atrophy, abundant amyloid plaques, a cytoskeletal Tau pathology and a loss of cholinergic neurons. While elderly mouse lemurs with normal brain aging maintain memory function and social interaction, animals with age-associated neurodegeneration lose their cognitive and social capacities and demonstrate certain similarities with age-associated human AD. We conclude that M. murinus is an interesting primate model for the study of normal brain aging and the biochemical dysfunctions occurring in age-associated neurodegeneration. Mouse lemurs might also become an increasingly important model for the development of novel treatments in this domain. [ABSTRACT FROM AUTHOR]

The solution conformation of the cyclic peptide J324 (cyclo[sup 0,6]-[Lys[sup 0],Glu[sup 6],D-Phe[sup 7]]BK), an antagonist targeted at the bradykinin (BK) B[sub 2] receptor, has been investigated using experimental and theoretical methods. In order to gain insight into the structural requirements essential for BK antagonism, we carried out molecular dynamics (MD) simulations using simulated annealing as the sampling protocol. Following a free MD simulation we performed simulations using nuclear Overhauser enhancement (NOE) distance constraints determined by NMR experiments. The low-energy structures obtained were compared with each other, grouped into families and analyzed with respect to the presence of secondary structural elements in their backbone. We also introduced new ways of plotting structural data for a more comprehensive analysis of large conformational sets. Finally, the relationship between characteristic backbone conformations and the spatial arrangement of specific pharmacophore centers was investigated. [ABSTRACT FROM AUTHOR]

Background Cold- and heat-induced urticaria are chronic physical urticaria conditions in which wheals, angioedema or both are evoked by skin exposure to cold and heat respectively. The diagnostic work up of both conditions should include skin provocation tests and accurate determination of critical temperature thresholds ( CTT) for producing symptoms in order to be able to predict the potential risk that each individual patient faces and how this may be ameliorated by therapy. Objective To develop and validate Temp Test ® 4, a simple and relatively inexpensive instrument for the accurate determination of CTT which may be used in clinical practice. Methods Temp Test ® 4 has a single 2 mm wide 350 mm U-shaped Peltier element generating a temperature gradient from 4 °C to 44 °C along its length. Using a clear plastic guide placed over the skin after provocation, CTT values may be determined with an accuracy of ±1 °C. Here, Temp Test ® 4 was compared with its much more expensive predecessor, Temp Test ® 3, in inducing wheals in 30 cold urticaria patients. Results Both Temp Test ® 4 and Temp Test ® 3 induced wheals in all 30 patients between 8 ° and 28 °C. There was a highly significant ( P < 0.0001) correlation between the instruments in the CTT values in individual patients. Conclusion The Temp Test ® 4 is a simple, easy to use, licensed, commercially available and affordable instrument for the determination of CTTs in both cold- and heat-induced urticaria. [ABSTRACT FROM AUTHOR]

Scattering from a one-dimensional random rough surface with Neumann boundary conditions is analyzed using a finite element formulation. Results are in excellent agreement with tapered-wave integral-equation solutions after averaging over realizations. Finite element advantages in CPU time, memory storage, and energy conservation tests are illustrated. [ABSTRACT FROM AUTHOR]

Investigates the rate of sucrose synthesis in cold-stored tubers. Measurement of the accumulation of sugars; Appearance of a form of sucrose phosphate synthase (SPS); Decrease of SPS expression that resulted in a reproducible but non-proportional decrease of soluble sugars in cold-stored tubers; Conclusion that SPS expression per se does not control sugar synthesis.

Antibodies raised against a peptide fragment (residues 60-456) of potato sucrose phosphate synthase (SPS) were used to investigate whether potato plants contain multiple forms of SPS. When a partially purified preparation of SPS from cold-stored potato tubers was separated on 5% polyacrylamide gel electrophoresis (PAGE), four immunopositive bands were found with estimated molecular weights of 125, 127, 135 and 145 kDa. These bands were also found in rapidly prepared extracts and were termed SPS-1a, SPS-1b, SPS-2 and SPS-3, respectively. Direct evidence that SPS-1a and SPS-1b represent active SPS was provided by the finding that both are greatly reduced in plants expressing an antisense sequence derived from the potato leaf SPS gene. SPS-2 was not decreased in the antisense plants, indicating that it has a significantly different sequence. Evidence that SPS-2 represents active SPS was obtained by showing that the amount of SPS-1a and SPS-1b protein remaining in the leaves and tubers of antisense potato plants was too low to account for the remaining SPS activity. The four immunopositive SPS forms had different tissue distributions. SPS-1a was the major form in all tissues except petals, sepals and stamens. SPS-1b and SPS-2 were absent in very young growing tissues but were present as minorforms in source leaves and sprouting tubers. The SPS-1b level was especially high in petals and sepals, and the SPS-2 level was especially high in the stamens. SPS-3 was only detected in very young tissues.The four forms also showed different responses to low temperature. Transfer of tubers to 4 °C led to a specific and reversible increase of SPS-1b during the next 4 d. The appearance of SPS-1b correlated with a change in the kinetic properties of SPS that has recently beenshown (Hill et al 1996) to play a key role in triggering the accumulation of sugars in cold-stored tubers. The appearance of SPS-1b protein at low temperature was accompanied by an increase of SPS transcrip... [ABSTRACT FROM AUTHOR]

This study explores the meaning of excellence in nursing care held by nurses. Qualitative data were collected from 156 undergraduate and postgraduate nurses by means of an open-ended questionnaire. Respondents were asked to reflect on practice which enabled a clear understanding of the meanings given to excellence in nursing care. In addition, details of their nursing background, level of nursing experience, and demographics were sought. Responses were content-analysed for themes by three coders. Four major themes emerged: (1) professionalism, (2) holistic care, (3) practice, (4) humanism. The fourth theme comprised three sub-themes: (a) enabling personal qualities, (b) nurse-patient relationships, and (c) nurse-health team relationships. Responses revealed that professionalism constituted an all-encompassing theme subsuming all others. Findings suggested that the client is the central focus of excellent nursing care at all times. According to these respondents, nurses who deliver excellent nursing care implement nursing in a professional and competent manner, demonstrate a holistic approach to caring, possess certain personal qualities which enhance practice, and relate to patients, families, peers, hospital administrators and community members in a competent, cooperative manner. An important aspect of this study is the differential quality of responses provided by respondents, who were students enrolled in a nursing degree programme compared to respondents who were state-registered nurses and concurrently undertaking higher degree studies. The final result is suggestive of the stages of transition through which nurses pass in their quest for excellence. [ABSTRACT FROM AUTHOR]

Background Platelet-activating factor ( PAF) causes wheal and flare responses which are abrogated by H1-antihistamines giving rise to the hypothesis that PAF-induced wheal development is secondary to histamine release from dermal mast cells. But is this hypothesis correct? Methods Wheal and flare responses were induced by intradermal injection of PAF, codeine and histamine in 14 healthy volunteers. Dermal histamine and PGD2 contractions were measured using microdialysis. Results PAF, unlike histamine and codeine, did not cause a statistically significant rise in mean histamine levels with ten persons showing negligible histamine release. Codeine caused a significant but variable histamine release, ranging from 29 to 282 ng/ml. Codeine, but not PAF or histamine, caused a small but statistically significant release of PGD2. Conclusion Wheal and flare reactions in human skin induced by PAF are not associated with histamine release and, therefore, appear to be independent of mast cell degranulation. [ABSTRACT FROM AUTHOR]

The article focuses on the pressure of standardized process of blood transfusion in Germany. Due to the decreasing numerous number of incapable donors of blood products, it costs pressures mainly in transfusion process. It is very expensive to gain a standardized procedure because it requires expensive devices like centrifuges and separators. One way of getting a high quality blood products is a bedside processing (BSP). BSP is the automated collection of blood products, with a high quality standardization and a high purity of the resulting product and a minimal number or no manual steps.

The article presents a case study of a 48-year-old Caucasian woman who was successfully treated with anti-immunoglobulin E (IgE) therapy after developing severe urticaria factitia. It states that she was treated with nonsedating antihistamines after her skin produced massive pruritus and whealing but none of the treatments have resulted in sufficient symptom control. However, when the anti-IgE treatment was performed, complete protection from symptom development was achieved.

The purpose herein is to report several examples in awake mammals of a dissociation between CO2-H+ ventilatory chemosensitivity and room air V1. We found in piglets that eupneic PaCO2 increased gradually from 26.5 ± 0.5 to 34.4 ± 1.2 between postnatal days (PN) 3-4 and PN 19-21 but CO2 sensitivity (expressed as V1 5% CO2/V1 room air) was unchanged between PN 3-4 and PN 19-21. In Sprague Dawley rats, we found that CO2 sensitivity was minimal between PN 0 and PN 14, but then it increased dramatically between PN 14 and PN 21, whereas room air V1/body weight decreased gradually from PN 0 to PN21. Finally, we found that in adult goats, neurotoxic lesioning of the rostral ventrolateral medulla, medullary raphe, and cerebellar fastigial nucleus (CFN) decreased CO2 sensitivity, but only increased eupneic PaCO2 by 2.0 ± 1.1, 0.2 ± 0.8, and 2.9 ± 0.3% respectively. Moreover, the CFN lesions doubled the day-to-day variability in CO2 sensitivity but did not alter variability of eupneic PaCO2. We conclude that under the conditions listed above, CO2-H+ ventilatory chemosensitivity is not a critical determinant of eupneic V1. [ABSTRACT FROM AUTHOR]

An abstract of the article "Electrophysiological effects after intramyocardial injection of mesenchymal vs. mononuclear bone marrow derived stem cells in the chronic ischaemic myocardium," by K. Krause and colleagues is presented.

The purpose of this study was to test the hypothesis that an intact cerebellar fastigial nucleus (CFN) is necessary for the hyperpnea of submaximal exercise. Bilateral stainless steel microtubules were implanted in the cerebellum inside (n = 12) or outside (n = 2) the CFN for injection (0.5 to 10 µl) of the neurotoxin ibotenic acid. All goats had difficulty maintaining normal posture and walking for up to one month after the implantation of the microtubules and again for hours or days after injecting the neurotoxin. As is typical for goats, prior to implantation of the microtubules the decrease in PaCO2 from rest during mild and moderate treadmill exercise was 2.0 ± 0.39 and 3.5 ± 0.45 mmHg, respectively. Implantation of the microtubules did not significantly change this exercise hyperventilation. However, neurotoxic lesioning with 10 µl ibotenic acid lesions significantly (P < 0.05) attenuated the decrease in PaCO2 by 1.3 and 2.8 mmHg at the first and second workload, respectively. The modest attenuation of the exercise hypocapnia at both workloads in CFN lesioned goats suggests that the CFN is part of the ventilatory control system that helps meet the gas exchange requirements of submaximal exercise. [ABSTRACT FROM AUTHOR]

Dialyzing mock cerebral spinal fluid (mCSF) equilibrated with 25% CO2 in the retrotrapezoid nucleus and the nucleus of the solitary tract of the awake rat increased inspiratory flow (VI) and tidal volume (VT) by 24 and 11%. In the awake goat, we found that dialyzing 25 and 80% CO2 at one site in the raphe increased VI and VT 8-10%, while dialyzing 50% in the rostral part of the cerebellar fastigial nucleus increased VI and VT 14-16%. The pre-Botzinger complex (PBC), a hypothesized respiratory rhythm generator, increased phrenic nerve activity after an acetazolamide-induced acidosis in the anesthetized cat. Thus, we tested the hypothesis that focal microdialysis (MD) of CO2/H+ in the PBC during wakfulness would stimulate breathing. Stainless steel microtubules were bilaterally implanted into the PBC of adult goats. Unilateral MD of mCSF equilibrated with 6.4% CO2 did not affect VI, VT or f. Unilateral MD of 25 or 50% CO2 did not affect VI or VT, but did significantly increase f by a maximum of 10% (P<0.05, n=12). Bilateral MD of 6.4 and 25% CO2 did not significantly affect VI, VT, or f. However, bilateral MD of 50% significantly increased f by a maximum of 8% (n<0.05, n=5), although VI and VT was unaffected. The findings that FA in the PBC of the awake goat affects only respiratory frequency lends support to the PBC's role in respiratory rhythm generation. Thus, our data suggests that the PBC may not only be instrinsically rhythmogenic, but chemosensitive as well. [ABSTRACT FROM AUTHOR]

Controversies regarding the role of pontine nuclei in the control of breathing and paucity of studies during physiologic conditions have prompted us to chronically implant microtubules (two unilateral and two bilateral) into the rostral pons of 4 goats. All goats recovered uneventfully and 3 weeks thereafter resting PaCO2 and CO2 sensitivity were near normal. Reverse microdialysis (MD) of atropine during the day (25, 50 or 100mM) or at night (25 or 50mM) affected absolute pulmonary ventilation (VI) in 3 of the 4 goats, as compared to MD with mock cerebral spinal fluid. In 2 goats, during the day, MD on one side and bilateral MD decreased VI, breathing frequency (f) and tidal volume (VT) but MD on the other side increased VI. In these goats, MD at night either had no effect or stabilized VI and f. In the other two goats, unilateral MD had no effect or increased VI during the day. In one of these goats, injection of atropine (5mM, 500nl or 1µl) increased V1, f and VT compared to mock injection. In all 4 goats, daytime MD did not stabilize VI, f or VT. Neither injection (5mM, 500nl or 1µl) nor MD (50mM) of atropine had any effect on CO2 sensitivity. These findings suggest that atropine delivered to the rostral pons acutely modulates ventilation in awake and asleep goats. [ABSTRACT FROM AUTHOR]